Our laboratory is investigating ways to improve the efficacy of tumor- infiltrating lymphocytes (TIL), and trying to delineate the mechanisms of their action in vivo. We have described that interleukin-6 incorporated into slow-release collagen matrix can generate TIL with enhanced in vivo activity. We have extended this to use tumor transduced with the gene for IL-6 as the means of local IL-6 delivery. In addition, we are studying the migration of TIL in response to various stimuli. We are proceeding with the purification of a novel tumor- produced protein with chemotactic activity for TIL and other activated CTL. We have achieved partial purification and have demonstrated that this factor differs from other described factors with chemotactic activity. In associated on-going clinical trials, we have shown that cyclophosphamide improves the localization of TIL to sites of tumor, and that this tumor homing is associated with clinical responses to TIL. Another clinical trial is investigating the efficacy of high-dose intensity IL-2 versus lower dose and dose intensity in a randomized, prospective trial in renal cell carcinoma. Other clinical trials have been initiated or are on-going in the treatment of adult soft tissue sarcomas. A randomized adjuvant chemotherapy trial using doxorubicin, ifosfamide and G-CSF has begun and another investigation of the role of radio-therapy for low-grade sarcomas is continuing.